Neurons are electrically excitable cells that process and transmit information around the nervous system. Neurons are the primary components of the brain and spinal cord in vertebrates, and ventral nerve cord in invertebrates.
Referring to FIG. 1, a neuron includes a nucleus as shown. The nucleus includes a soma, an axon, and a dendrite. The soma acts as a processing unit for processing of neuronal signals and is responsible for generating action potentials (i.e., voltages). Action potentials (also referred to as electrical signals herein) are further described below. The action potentials are propagated from the soma, through an axon, to the end of the neuron, which is also called an axon terminal. In the axon terminal, chemical neurotransmitters that chemically encode the electrical signal are produced, which cross a gap between the axon terminal and a dendrite of another neuron (not shown). This gap is part of the connection system of two neurons. The gap is referred to as a synapse. The synapse is described more fully below in conjunction with FIG. 2.
Referring now to FIG. 2, a synaptic cleft is formed between two neurons, and in particular, between an axon terminal of one neuron and a dendritic spine of another neuron. Electrical signals tend to propagate from the top to the bottom of this figure.
A synapse has three main parts, the axon terminal that contains the neurotransmitters, the synaptic cleft, and the dendritic spine.
As described more fully below, neurotransmitters generated by the pre-synaptic neuron (axon terminal), and which cross the synapse, bind to neurotransmitter receptors (also called input receptors herein) on the dendrite of the postsynaptic neuron. Every neuron has multiple dendrites that are all connected to other neurons. Current signals that propagate into the dendrites, also referred to as postsynaptic currents, form postsynaptic potentials that are summed at the soma of the post-synaptic neuron to produce new action potentials.
An action potential (also referred to herein as a spike or pulse) is a self-regenerating wave of electrochemical activity that allows excitable cells (such as muscle and nerve cells) to carry a signal over a distance. It is the primary electrical signal generated by nerve cells, and arises from changes in the permeability of the nerve cell's axonal membranes to specific ions. Action potentials are pulse-like waves of voltage that travel along several types of cell membranes. An exemplary action potential is generated on the membrane of the axon of a neuron, but also appears in other types of excitable cells, such as cardiac muscle cells, and even plant cells.
A typical action potential is initiated at the axon when the membrane is sufficiently depolarized (i.e., when its voltage is sufficiently increased). As the membrane potential is increased, both sodium and potassium ion channels begin to open. This increases both the inward sodium current (depolarization) and the balancing outward potassium current (repolarization/hyperpolarization). For small voltage increases, the potassium current triumphs over the sodium current and the voltage returns to its normal resting value, typically −70 mV. However, if the voltage increases past a critical threshold, typically 15 mV higher than the resting value, the sodium current dominates. This results in a runaway condition whereby the positive feedback from the sodium current activates even more sodium channels. Thus, the cell “fires,” producing an action potential.
Synapses are special junctions that enable two neurons to communicate with each other. Synapses allow neurons to form interconnected circuit networks within the nervous system and are very crucial to the biological computations that underlie perception, thought, and memory. Synapses also provide the means for the nervous system to connect and control other systems of the body. For instance, a specialized synapse between a motor neuron and a muscle cell is called a neuromuscular junction.
Signal propagation through the synapse is promoted by release of neurotransmitters. In the axon terminal are vesicles containing neurotransmitters. The vesicles are able to release the neurotransmitters when stimulated. Arrival of an action potential into the axon terminal (e.g., from above in FIG. 2) results in an influx of calcium [Ca] ions from around the neuron. Influx of calcium into the axon terminal triggers a biochemical process that results to the release of neurotransmitters (e.g., glutamate) from the vesicles to the synaptic cleft about 180 microseconds after [Ca] influx.
As used herein, the brackets, [ ], are representative of an intracellular substance. As used herein, the nomenclature [Ca2+] is used interchangeably with the nomenclature [Ca].
Receptors on the dendrite spine bind to the neurotransmitter molecules and respond by opening nearby ion channels in the post-synaptic cell membrane, causing ions to rush in or out via ion channels, forming postsynaptic currents that change the local membrane potential (i.e., voltage) of the postsynaptic cell. The resulting change in voltage is called postsynaptic potential. In general, the result is an excitatory postsynaptic potential (EPSP), in the case of depolarizing excitatory postsynaptic currents (EPSC), or an inhibitory postsynaptic potential (IPSP), in the case of hyperpolarizing inhibitory postsynaptic currents (IPSC). Whether a synapse is excitatory or inhibitory depends on what type of ion channels are opened to conduct the postsynaptic current, which in turn is a function of the type of receptors and neurotransmitters employed at the synapse.
The last stage of signaling is termination. Presynaptic signals are terminated by the breakdown or reuptake of existing neurotransmitters. Reuptake is mainly localized in the presynaptic neuron and serves to recycle transported neurotransmitters.
The so-called “strength” of a synapse is related to a change in postsynaptic current resulting from activation of postsynaptic neurotransmitter receptors. Changes in synaptic strength can be short term (short term potentiation/depression, or STP/STD), which causes no permanent structural changes in the neuron. Typically, this change lasts a few seconds to minutes. Sometimes, strength changes are long term (long term potentiation/depression, or LTP/LTD). For these types of changes, repeated or continuous synaptic activation results in an alteration of the structure of the synapse itself. Learning and memory are believed to result from long term changes in synaptic strength, via a so-called “synaptic plasticity” mechanism.
The concept of synaptic strength leads to the notion of a strong synapse as differentiated from a weak synapse. For a strong synapse, an action potential in the presynaptic neuron triggers another action potential in the post-synaptic neuron. Conversely, for a weak synapse, an EPSP may not reach the threshold for action potential initiation in the post-synaptic neuron.
Each neuron forms synapses with many other neurons and therefore receives multiple synaptic inputs. When action potentials fire simultaneously in several of these neurons, multiple EPSCs are created which all generate EPSPs that sum up in the soma. Hence, the output of a neuron may depend on the input of many others, each of which may have a different degree of influence, depending on the strength of its synapse with a specific neuron.
It would be desirable to provide a circuit that can emulate the above-described operation of a neuron in real-time.